Amplification of CDK4 and MDM2 in malignant melanoma
Amplification of CDK4 and MDM2 in malignant melanoma
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DOI：
10.1002/gcc.20310
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发表时间：
2006-05-01
影响因子：
3.7
通讯作者：
Bosenberg, MW
中科院分区：
文献类型：
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作者：
Muthusamy, V;Hobbs, C;Bosenberg, MW
12q 13-15 区域的扩增是多种人类肿瘤（包括脂肪肉瘤、神经胶质瘤和骨肉瘤）中的常见事件。我们已经在未培养的恶性黑色素瘤子集中（53 个中的 3 个）证明了 12q 14 的高水平扩增。使用定量 PCR 对扩增子进行高分辨率图谱显示，二分扩增子由以 CDK4 为中心的初级 50-kb 扩增子和以 MDM2 为中心的次级扩增子组成，而没有扩增中间的 11 Mb 基因组 DNA。对 12q 14 扩增的黑色素瘤中 mRNA 和蛋白质水平的分析表明，靶基因 CDK4 和 MDM2 过度表达，而 CDKN2A-P16 (P16INK4A) 或 CDKN2A-P14ARF (P14ARF) 表达没有丢失，而 CDKN2A-P16 (P16INK4A) 或 CDKN2A-P14ARF (P14ARF) 表达是 RBI 和 TP53 通路的重要调节因子，在黑色素瘤中通常丢失或突变。这些结果表明，CDK4 和 MDM2 的共扩增可能替代黑色素瘤子集中 P16INK4A 和 P14ARF 功能的丧失。 (c) 2006 Wiley-Liss, Inc.
Amplification of the 12q 13-15 region is a common event in several human tumors including liposarcomas, gliomas, and osteosarcomas. We have demonstrated high-level amplification of 12q 14 in a subset of uncultured malignant melanomas (3 of 53). High-resolution mapping of the amplicon using quantitative PCR revealed a bipartite amplicon consisting of a primary 50-kb amplicon centered on CDK4 and a secondary amplicon centered on MDM2, without amplification of the intervening 11 Mb of genomic DNA. Analysis of mRNA and protein levels in melanomas with 12q 14 amplification demonstrated overexpression of target genes CDK4 and MDM2 without loss of CDKN2A-P16 (P16INK4A) or CDKN2A-P14ARF (P14ARF) expression, important regulators of the RBI and TP53 pathways, which are commonly lost or mutated in melanoma. These results suggest that coamplification of CDK4 and MDM2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas. (c) 2006 Wiley-Liss, Inc.